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Abstract Early patterning of DNA methylation (DNAm) may play an important role in later disease development. To better understand intergenerational epigenetic inheritance, we investigated the correlation between DNAm in blood in mother-newborn and in father-newborn pairs in the Isle of Wight (IoW) birth cohort. For parent-newborn pairs (n = 48), offspring DNAm was measured in cord blood and the parent’s DNAm in whole blood. Mothers’ DNAm was analyzed at birth (Guthrie card), age 18, early and late pregnancy respectively, and fathers’ DNAm was measured during the mother’s pregnancy. Linear regressions were applied to assess the intergenerational correlation of parental DNAm with that of offspring. Among various pairs of mother-newborn and father-newborn DNAm, the pairs where the mothers’ DNAm was measured at age 18 years exhibited the highest number of CpGs with significant intergenerational correlation in DNAm, with 1829 CpGs (0.54%) of the 338,526 CpGs studied (FDR

Abstract Background An increasing number of clinical studies have begun to explore combination strategies with immune checkpoint inhibitors, aiming to present new opportunities for overcoming anti-PD-1 treatment resistance in gastric cancer. Unfortunately, the exploration of certain immune checkpoint inhibitor combination strategies has yielded suboptimal results. Therefore, it is necessary to comprehensively analyze the expression patterns of immune checkpoints and identify optimal combination regimens of anti-PD-1 inhibitors with other immune checkpoint inhibitors. Methods Leveraging single-cell RNA sequencing (scRNA-seq) and multivariate linear regression interaction models, we dissected the immune checkpoint expression characteristics of CD8+ T cells in gastric cancer and the immune checkpoint expression pattern (ICEP) mediating anti-PD-1 treatment resistance. Furthermore, we employed transcription factor analysis and CellOracle to explore the transcriptional regulatory mechanisms governing CD8+ T cell differentiation fates. Finally, we utilized Nichenet and spatial transcriptomic analysis to investigate the spatial expression patterns of immune checkpoints. Results Interaction analysis indicated that, among the known immune checkpoints, co-expression of NKG2A and PD-1 might exert a more profound inhibitory effect on the proliferative capacity of CD8+ T cells. The co-expression analysis revealed differential co-expression pattern of PD-1 and NKG2A, defined as ICEP1 (CD8+ T cells co-expressing PD-1, CTLA-4, TIGIT, LAG-3 or CD38) and ICEP2 (CD8+ T cells solely expressing NKG2A or co-expressing with other immune checkpoints), reflecting the co-occurrence pattern of PD-1 and the mutual exclusivity of NKG2A. Further, these two ICEP CD8+ T cell subsets represented distinct CD8+ T cell differentiation fates governed by MSC and RUNX3. Notably, ICEP2 CD8+ T cells were associated with anti-PD-1 therapy resistance in gastric cancer. This phenomenon may be attributed to the recruitment of LGMN+ macrophages mediated by the CXCL16-CXCR6 signaling pathway. Conclusion This study unveiled two distinct ICEPs and the mutually exclusivity and co-occurrence characteristics of CD8+ T cells in gastric cancer. The ICEP2 CD8+ T cell subset, highly expressed in gastric cancer patients resistant to anti-PD-1 therapy, may be recruited by LGMN+ macrophages through CXCL16-CXCR6 axis. These findings provide evidence for NKG2A as a novel immunotherapeutic target in gastric cancer and offer new insights into combination strategies for immune checkpoint inhibitors in gastric cancer. Graphical Abstract

Abstract FVP is a polysaccharide extracted from Flammulina velutipes with immunomodulatory, anti-tumor, and anti-oxidation activities. In this study, we obtained the crude polysaccharide FVP-C from the water extract of Flammulina velutipes, and its main component FVP-S1 was obtained after further purification. Upon structural identification, we found that FVP-C is a neutral polysaccharide, and FVP-S1 was an acidic golden mushroom polysaccharide, consisting of glucuronic acid, xylose, and glucose. Lung adenocarcinoma (A549) was treated with FVP-S1 and FVP-C, respectively, and we found that FVP-S1 and FVP-C inhibited the proliferation and migration ability of tumor cells, as well as changed the morphology of the tumor cells and caused chromosome sheteropythosis, among which FVP-S1 had the best inhibition effect. The results of flow cytometry experiments and mitochondrial membrane potential, RT-qPCR, and Western blot showed that FVP-S1 and FVP-C were able to decrease the mitochondrial membrane potential, increase the expression level of apoptotic proteins Casepase-3 and Casepase-9 proteins, and at the same time, increase the ratio of Bax and Bcl-2, which promoted apoptosis of tumor cells. In conclusion, these data indicated that FVP-S1 and FVP-C were able to induce apoptosis in A549 cells through the mitochondrial pathway, which played an important role in inhibiting tumor cells.

Background The heterogeneity of myelodysplastic syndromes (MDS) is strong, with poor efficacy of existing therapeutic regimens and large individual differences in patient prognosis. B-cell lymphomato-2 (Bcl-2) protein is highly expressed in patients with myeloid tumors, which has been proved by previous to be associated with disease progression, chemotherapy resistance, and shortened overall survival. The Bcl-2 inhibitor Veneckla (VEN) is approved for elderly patients with newly diagnosed acute myeloid leukemia (AML) who are not eligible for intensive therapy, and there is less data on its use in MDS patients. The difference in Bcl-2 expression in MDS patients and its correlation with the efficacy and prognosis of VEN therapy haven't been reported. Objective To analyse the expression of Bcl-2 protein in MDS patients and assess its correlation with the efficacy and prognosis of VEN treatment. Methods The clinical data of 71 patients with MDS admitted to Sichuan Academy of Medical Sciences·Sichuan Provincial People's Hospital from July 2018 to December 2022 were retrospectively analyzed. Baseline data of patients including gender, age, blood routine, blood biochemistry, bone marrow hemocytology, flow cytometry, chromosome karyotype, myeloid gene mutation, fusion gene mutation and MDS-EB typing were collected. The expression of Bcl-2 protein was detected by immunohistochemical staining. According to the modified International Prognostic Score System (IPSS-R), the patients were divided into 5 risk levels of very low risk (0 case), low risk (1 case), medium risk (7 cases), high risk (40 cases) and very high risk (23 cases). Patients with bone marrow Bcl-2 positivity≥10% were defined as Bcl-2 positive and0.05) . Conclusion Bcl-2 protein contributes to MDS fusion gene mutation and myeloid gene mutation; Bcl-2 positive expression was not associated with the survival of MDS patients. There was no difference in survival rate between Bcl-2 positive and Bcl-2 negative patients who received the VA combination regimen.

Background The bark of Chinese fir (Cunninghamia lanceolata), the largest afforestation tree species in the forest areas of southern China, is susceptible to injuries and bites from small animals. The population of small animals has recently increased owing to improvements in the ecological environment across various forested areas, thus increasing the incidence of injuries in the bark of Chinese fir. Following such injuries, the bark secretes light yellow or milky white secretions, the function of which remains unclear. The present study aimed to reveal the antibacterial effect of exudates of different Chinese fir cultivars on five bacterial species. Methods The research involved three-year-old plantations of Taxus chinensis var. koraiensis and Yangkou3 and three-year-old container plantations of Taxus chinensis var. pendula, Yang 061, and Yang 020. The antibacterial effects of exudates were analyzed using the filter paper diffusion method. The minimum inhibitory concentration for each secretion and the bacterial inhibition zone were determined. Results The exudates of the different Chinese fir bark exhibited notable antibacterial effects on Bacillus subtilis, Salmonella paratyphi B, Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus. However, the extent of these antibacterial effects varied among the different Chinese fir cultivars, as the minimum inhibitory concentrations (MICs) of the exudates against the five bacterial species varied. The mean MIC of Pseudomonas aeruginosa was lower potency, whereas that of Escherichia coli was the lowest. Notably, the antibacterial efficacy of the exudates was mainly influenced by the composition of the secretions rather than the number of secretions, with organic acid compounds and terpenoids potentially contributing to the antibacterial effects against E. coli and Bacillus subtilis, respectively. Conclusion This study demonstrates the antibacterial effect of wound secretion of different Chinese fir cultivars, highlighting their varying efficacy on different bacterial species. Moreover, the antibacterial ability of the exudates of the strains was mainly determined by the composition of the wound secretions, and there was no noticeable relationship with the number of wound secretions. The results of this study offers a theoretical basis for screen Chinese fir cultivars with high-disease-resistant.

Abstract Mouse auditory cortex is composed of six sub-fields: primary auditory field (AI), secondary auditory field (AII), anterior auditory field (AAF), insular auditory field (IAF), ultrasonic field (UF) and dorsoposterior field (DP). Previous studies have examined thalamo-cortical connections in the mice auditory system and learned that AI, AAF, and IAF receive inputs from the ventral division of the medial geniculate body (MGB). However, the functional and thalamo-cortical connections between nonprimary auditory cortex (AII, UF, and DP) is unclear. In this study, we examined the locations of neurons projecting to these three cortical sub-fields in the MGB, and addressed the question whether these cortical sub-fields receive inputs from different subsets of MGB neurons or common. To examine the distributions of projecting neurons in the MGB, retrograde tracers were injected into the AII, UF, DP, after identifying these areas by the method of Optical Imaging. Our results indicated that neuron cells which in ventral part of dorsal MGB (MGd) and that of ventral MGB (MGv) projecting to UF and AII with less overlap. And DP only received neuron projecting from MGd. Interestingly, these three cortical areas received input from distinct part of MGd and MGv in an independent manner. Based on our foundings these three auditory cortical sub-fields in mice may independently process auditory information.

Abstract Pancreatic neuroendocrine tumors (PanNETs), though uncommon, have a high likelihood of spreading to other body parts. Previously, the genetic diversity and evolutionary patterns in metastatic PanNETs were not well understood. To investigate this, we performed multiregion sampling whole-exome sequencing (MRS-WES) on samples from 10 patients who had not received prior treatment for metastatic PanNETs. This included 29 primary tumor samples, 31 lymph node metastases, and 15 liver metastases. We used the MSK-MET dataset for survival analysis and validation of our findings. Our research indicates that mutations in the MEN1/DAXX genes might trigger the early stages of PanNET development. We categorized the patients based on the presence (MEN1/DAXX mut, n = 7) or absence (MEN1/DAXX wild, n = 3) of these mutations. Notable differences were observed between the two groups in terms of genetic alterations and clinically relevant mutations, confirmed using the MSK-MET dataset. Notably, patients with mutations in MEN1/DAXX/ATRX genes had a significantly longer median overall survival compared to those without these mutations (median not reached vs. 43.63 months, p = 0.047). Multiplex immunohistochemistry (mIHC) analysis showed a more prominent immunosuppressive environment in metastatic tumors, especially in patients with MEN1/DAXX mutations. These findings imply that MEN1/DAXX mutations lead PanNETs through a unique evolutionary path. The disease’s progression pattern indicates that PanNETs can spread early, even before clinical detection, highlighting the importance of identifying biomarkers related to metastasis to guide personalized treatment strategies.

Objective(s): Inadequate cytotrophoblast migration and invasion are speculated to result in preeclampsia, which is a pro-inflammatory condition. Sodium dichloroacetate (DCA) exerts anti-inflammatory actions. Thus,we sought to investigate the effect of DCA on the migration function of the lipopolysaccharide (LPS)-stimulated human-trophoblast-derived cell line (HTR-8/SVneo).Materials and Methods: HTR-8/SVneo cells were treated with LPS to suppress cell migration. Cell migration was examined by both scratch wound healing assay and transwell migration assay. Western blotting was used to analyze the expression levels of toll-like receptor-4 (TLR4), nuclear factor-κB (NF-κB), TNF-α, IL-1β, and IL-6 in the cells.Results: DCA reversed LPS-induced inhibition of migration in HTR-8/SVneo cells. Furthermore, DCA significantly suppressed LPS-induced activation of TLR4, phosphorylation of NF-κB (p65), translocation of p65 into the nucleus, and the production of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6). Treatment with inhibitors of TLR4 signal transduction (CLI095 or MD2-TLR-4-IN-1) reduced LPS-induced overexpression of pro-inflammatory cytokines, and a synergistic effect was found between TLR4 inhibitors and DCA in HTR-8/SVneo cells. Conclusion: DCA improved trophoblast cell migration function by suppressing LPS-induced inflammation, at least in part, via the TLR4/NF-κB signaling pathway. This result indicates that DCA might be a potential therapeutic candidate for human pregnancy-related complications associated with trophoblast disorder.

Abstract Background Little is known about the effects of night shifts and their interactions with genetic factors on chronic obstructive pulmonary disease (COPD). In this study, we aim to investigate relationships between long-term night shift work exposure and COPD risk, and assess modification effects of genetic predisposition. Methods A total of 277,059 subjects who were in paid employment or self-employed were included in the UK Biobank. Information on current and lifetime employment was obtained, and a weighted COPD-specific genetic risk score (GRS) was constructed. We used Cox proportional hazard models to investigate associations between night shift work and COPD risk, and their interaction with COPD-specific GRS. Results The cohort study included 277,059 participants (133,063 men [48.03%]; mean [SD] age, 52.71 [7.08] years). During a median follow-up of 12.87 years, we documented 6558 incidents of COPD. From day work, irregular night shifts to regular night shifts, there was an increased trend in COPD incidence (P for trend 8 nights/month) were associated with a higher COPD risk. Additionally, there was an additive interaction between night shifts and genetic susceptibility on the COPD risk. Subjects with permanent night shifts and high genetic risk had the highest risk of COPD (HR: 1.90 [95% CI: 1.63, 2.22]), with day workers with low genetic risk as a reference. Conclusions Long-term night shift exposure is associated with a higher risk of COPD. Our findings suggest that decreasing the frequency and duration of night shifts may offer a promising approach to mitigating respiratory disease incidence in night shift workers, particularly in light of individual susceptibility.

Abstract Background The cancer-immunity cycle (CI cycle) provides a theoretical framework to illustrate the process of the anticancer immune response. Recently, the update of the CI cycle theory emphasizes the importance of tumor’s immunological phenotype. However, there is lack of immunological phenotype of pan-cancer based on CI cycle theory. Methods Here, we applied a visualizing method termed ‘cancer immunogram’ to visualize the state of CI cycle of 8460 solid tumors from TCGA cohort. Unsupervised clustering of the cancer immunogram was performed using the nonnegative matrix factorization (NMF) analysis. We applied an evolutionary genomics approach (dN/dS ratio) to evaluate the clonal selection patterns of tumors with distinct immunogram subtypes. Results We defined four major CI cycle patterns across 32 cancer types using a cancer immunogram approach. Immunogram-I was characterized by ‘hot’ and ‘exhausted’ features, indicating a favorable prognosis. Strikingly, immunogram-II, immunogram-III, and immunogram-IV represented distinct immunosuppressive patterns of ‘cold’ tumor. Immunogram-II was characterized by ‘cold’ and ‘radical’ features, which represented increased expression of immune inhibitor molecules and high levels of positive selection, indicating the worst prognosis. Immunogram-III was characterized by ‘cold’ and ‘recognizable’ features and upregulated expression of MHC I molecules. Immunogram-IV was characterized by ‘cold’ and ‘inert’ features, which represented overall immunosuppression, lower levels of immunoediting and positive selection, and accumulation of more tumor neoantigens. In particular, favorable overall survival was observed in metastatic urothelial cancer patients with immunogram-I and immunogram-IV after immune checkpoint inhibitor (ICI) therapy. Meanwhile, a higher response rate to ICI therapy was observed in metastatic gastric cancer patients with immunogram-I phenotype. Conclusions Our findings provide new insight into the interaction between immunity and cancer evolution, which may contribute to optimizing immunotherapy strategies.

Abstract The Hedyotis diffusa–Scutellaria officinalis pair (HD–SB) has therapeutic effects on a variety of cancers. Our study was to explore the mechanism of HD–SB in the treatment of hepatocellular carcinoma (HCC). A total of 217 active ingredients of HD–SB and 1196 HCC-related targets were reserved from the TCMSP and the SwissTarget Prediction database, and we got 63 intersection targets from GeneCards. We used a Venn diagram, and Cytoscape found that the three core ingredients were quercetin, luteolin, and baicalein. The PPI analysis showed that the core targets were TP53, CDK2, XPO1, and APP. Molecular docking results showed that these core ingredients had good binding potential with the core targets. HD–SB acts simultaneously on various HCC-related signaling pathways, including proteoglycans in cancer and the P53 signaling pathway. In vitro experiments confirmed that HD–SB can inhibit HepG2 cell proliferation by increasing TP53 and APP levels and decreasing XPO1 and CDK2 levels. This study analyzed active ingredients, core targets, and central mechanisms of HD–SB in the treatment of HCC. It reveals the role of HD–SB in targeting the P53 signaling pathway in the treatment of HCC. We hope that our research could provide a new perspective to the therapy of HCC and find new anticancer drugs.

Abstract Background Although the molecular features of pancreatic ductal adenocarcinoma (PDAC) have been well described, the impact of detailed gene mutation subtypes on disease progression remained unclear. This study aimed to evaluate the impact of different TP53 mutation subtypes on clinical characteristics and outcomes of patients with PDAC. Methods We included 639 patients treated with PDAC in Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine between Jan 2019 and Jun 2021. The genomic alterations of PDAC were analyzed, and the association of TP53 mutation subtypes and other core gene pathway alterations with patients’ clinical characteristics were evaluated by Chi-squared test, Kaplan-Meier method and Cox regression model. Results TP53 missense mutation was significantly associated with poor differentiation in KRASmut PDAC (50.7% vs. 36.1%, P = 0.001). In small-sized (≤ 2 cm) KRASmut tumors, significantly higher LNs involvement (54.8% vs. 23.5%, P = 0.010) and distal metastic rate (20.5% vs. 2.9%, P = 0.030) were observed in those with TP53 missense mutation instead of truncating mutation. Compared with TP53 truncating mutation, missense mutation was significantly associated with reduced DFS (6.6 [5.6–7.6] vs. 9.2 [5.2–13.3] months, HR 0.368 [0.200–0.677], P = 0.005) and OS (9.6 [8.0-11.1] vs. 18.3 [6.7–30.0] months, HR 0.457 [0.248–0.842], P = 0.012) in patients who failed to receive chemotherapy, while higher OS (24.2 [20.8–27.7] vs. 23.8 [19.0–28.5] months, HR 1.461 [1.005–2.124], P = 0.047) was observed in TP53missense cases after chemotherapy. Conclusions TP53 missense mutation was associated with poor tumor differentiation, and revealed gain-of-function properties in small-sized KRAS transformed PDAC. Nonetheless, it was not associated with insensitivity to chemotherapy, highlighting the neoadjuvant therapy before surgery as the potential optimized strategy for the treatment of a subset of patients.

Background Studies have shown that chronic exposure to job stress may increase the risk of sleep disturbances and that hypothalamic‒pituitary‒adrenal (HPA) axis gene polymorphisms may play an important role in the psychopathologic mechanisms of sleep disturbances. However, the interactions among job stress, gene polymorphisms and sleep disturbances have not been examined from the perspective of the HPA axis. This study aimed to know whether job stress is a risk factor for sleep disturbances and to further explore the effect of the HPA axis gene × job stress interaction on sleep disturbances among railway workers. Methods In this cross-sectional study, 671 participants (363 males and 308 females) from the China Railway Fuzhou Branch were included. Sleep disturbances were evaluated with the Pittsburgh Sleep Quality Index (PSQI), and job stress was measured with the Effort-Reward Imbalance scale (ERI). Generalized multivariate dimensionality reduction (GMDR) models were used to assess gene‒environment interactions. Results We found a significant positive correlation between job stress and sleep disturbances (P < 0.01). The FKBP5 rs1360780-T and rs4713916-A alleles and the CRHR1 rs110402-G allele were associated with increased sleep disturbance risk, with adjusted ORs (95% CIs) of 1.75 [1.38–2.22], 1.68 [1.30–2.18] and 1.43 [1.09–1.87], respectively. However, the FKBP5 rs9470080-T allele was a protective factor against sleep disturbances, with an OR (95% CI) of 0.65 [0.51–0.83]. GMDR analysis indicated that under job stress, individuals with the FKBP5 rs1368780-CT, rs4713916-GG, and rs9470080-CT genotypes and the CRHR1 rs110402-AA genotype had the greatest risk of sleep disturbances. Conclusions Individuals carrying risk alleles who experience job stress may be at increased risk of sleep disturbances. These findings may provide new insights into stress-related sleep disturbances in occupational populations.

The traditional Chinese medicine (TCM) bupleurum-ginger-licorice formula presents significant anti-cancer effects, but its active ingredients and inhibitory mechanism remain unclear. In this work, the core effective ingredient quercetin and its signal transducer and activator of transcription 3 (Stat3) receptor both were identified by network pharmacology. Quercetin is a low-toxicity, non-carcinogenic flavonoid with antioxidant, anti-inflammatory and anticancer activities, which is widely distributed in edible plants. Stat3 can bind to specific DNA response elements and serves as a transcription factor to promote the translation of some invasion/migration-related target genes, considered as a potential anticancer target. Here, molecular docking and molecular dynamics (MD) simulation both were used to explore molecular recognition of quercetin with Stat3. The results show that quercetin impairs DNA transcription efficiency by hindering Stat3 dimerization, partially destroying DNA conformation. Specifically, when the ligand occupies the SH2 cavity of the enzyme, spatial rejection is not conductive to phosphokinase binding. It indirectly prevents the phosphorylation of Y705 and the formation of Stat3 dimer. When the inhibitor binds to the DT1005 position, it obviously shortens the distance between DNA and DBD, enhances their binding capacity, and thereby reduces the degree of freedom required for transcription. This work not only provides the binding modes between Stat3 and quercetin, but also contributes to the optimization and design of such anti-cancer inhibitors.

BackgroundFoliage color is considered an important ornamental character of Cymbidium tortisepalum (C. tortisepalum), which significantly improves its horticultural and economic value. However, little is understood on the formation mechanism underlying foliage-color variations.MethodsIn this study, we applied a multi-omics approach based on transcriptomics and metabolomics, to investigate the biomolecule mechanisms of metabolites changes in C. tortisepalum colour mutation cultivars.ResultsA total of 508 genes were identified as differentially expressed genes (DEGs) between wild and foliage colour mutation C. tortisepalum cultivars based on transcriptomic data. KEGG enrichment of DEGs showed that genes involved in phenylalanine metabolism, phenylpropanoid biosynthesis, flavonoid biosynthesis and brassinosteroid biosynthesis were most significantly enriched. A total of 420 metabolites were identified in C. tortisepalum using UPLC-MS/MS-based approach and 115 metabolites differentially produced by the mutation cultivars were identified. KEGG enrichment indicated that the most metabolites differentially produced by the mutation cultivars were involved in glycerophospholipid metabolism, tryptophan metabolism, isoflavonoid biosynthesis, flavone and flavonol biosynthesis. Integrated analysis of the metabolomic and transcriptomic data showed that there were four significant enrichment pathways between the two cultivars, including phenylalanine metabolism, phenylpropanoid biosynthesis, flavone and flavonol biosynthesis and flavonoid biosynthesis.ConclusionThe results of this study revealed the mechanism of metabolites changes in C. tortisepalum foliage colour mutation cultivars, which provides a new reference for breeders to improve the foliage color of C. tortisepalum.

Abstract Immunocompromised individuals are particularly vulnerable to viral infections and reactivation, especially endogenous herpes viruses such as Epstein-Barr virus (EBV), a member of oncogenic gamma-herpesviruses, which are commonly linked to pneumonia and consequently significant morbidity and mortality. In the study of human and animal oncogenic gammaherpesviruses, the murine gamma-herpesviruses-68 (MHV-68) model has been applied, as it can induce pneumonia in immunocompromised mice. Mesenchymal stem cell (MSC) treatment has demonstrated therapeutic potential for pneumonia, as well as other forms of acute lung injury, in preclinical models. In this study, we aim to investigate the therapeutic efficacy and underlying mechanisms of human bone marrow-derived MSC (hMSC) on MHV-68-induced pneumonia. We found that intravenous administration of hMSCs significantly reduced lung damages, diminished inflammatory mediators and somehow inhibited MHV-68 replication. Furthermore, hMSCs treatment can regulate innate immune response and induce macrophage polarization from M1 to M2 phenotype, could significantly alter leukocyte infiltration and reduce pulmonary fibrosis. Our findings with co-culture system indicated that hMSCs effectively reduced the secretion of of inflammation-related factors and induced a shift in macrophage polarization, consistent with in vivo results. Further investigations revealed that hMSCs treatment suppressed the activation of macrophage ROS/NLRP3 signaling pathway in vivo and in vitro. Moreover, administration of MCC950, a selective NLRP3 inhibitor has been shown to effectively reduce ROS production and subsequently alleviate inflammation induced by MHV-68. Taken together, our work has shown that hMSCs can effectively protect mice from lethal MHV-68 pneumonia, which may throw new light on strategy for combating human EBV-associated pneumonia.

Objective To investigate the demographic characteristics and factors affecting the willingness to donate blood among potential donors in China, so as to improve the recruitment efficiency for blood donors. Methods Non-blood donors aged 18-55 were investigated by online questionnaire to collect data in terms of sociodemographic characteristics (10 items), blood donation related behaviors (9 items), blood donation willingness and factors affecting their willingness (5 items) from October to December 2022. Logistic regression analysis was utilized to investigate their demographic characteristics, and linear regression analysis was used to explore the factors influencing their donation willingness. Results Logistic regression analysis was conducted with potential blood donors as dependent variable, revealed that individuals who were not only-child 59.6%(334/560) vs 45.4%(98/216), had friends received blood transfusion 63.8%(238/373) vs 48.3%(194/402), had relatives with blood donation experience 63.0%(194/308) vs 51.0%(238/467), and received blood donation information from relatives or friends 64.4%(152/236) vs 51.9%(280/539) were more likely to be potential donors(P0.05). While subjective norms, convenience of blood donation and personal empathy had positive effects on willingness to donate blood, the regression coefficients were all greater than 0, which were 0.58, 0.14 and 0.34 (P

Background Multiple myeloma (MM) is a common hematologic malignancy. With the emergence of a variety of new drugs, the survival rates of patients have increased, however, further discussion on how to achieve deeper and faster remission and reduce recurrence of patients is still needed. Objective To investigate the efficacy and safety of daratumumab in the chemotherapy of MM. Methods 73 MM patients treated with daletumab in Sichuan Provincial People's Hospital from January 2020 to July 2022 were included as study subjects. Baseline information of the included patients were collected through the electronic medical record system. All patients were treated with daletumab based regimen and followed up through outpatient and inpatient review and telephone once a month when it is not time for review, with the time of first use of darettuzumab since 2020-01-01 as the starting point, death, disease recurrence or end of follow-up as the ending point. Follow-up was up to 2022-07-31 with a median follow-up time of 6.5 (0.5, 26.5) months. Overall response rate (ORR) and complete response rate were used to evaluate the efficacy of the patients. Kaplan-Meier curves were plotted for different drug use, initial renal function, drug administration, cytogenetic risk stratification and M protein types, and compared by Log-rank test. Results The median age of the patients was 64 (30, 86) years, including 38 males and 35 females. 28 MM patients were treated with first-line darettuzumab, 13 were switched from other regiments to darettuzumab due to adverse reactions, and 32 patients had relapsed and refractory multiple myeloma (RRMM). 18 patients were lost during follow-up, and a total of 55 patients were available for efficacy assessment. After one course of treatment with the darettuzumab-based chemotherapy regimen, ORR was 72.7% with the complete response rate of 30.9%, including 3.6% (2/55) achieved strin-gent complete response (sCR) and 27.3% (15/55) achieved complete response (CR), 10.9% (6/55) achieved very good partial response (VGPR), 30.9% (17/55) achieved partial response (PR), 9.1% (5/55) achieved minimal response (MR), 12.7% (7/55) achieved stable disease (SD), and 5.5% (3/55) achieved disease progression (PD). The median progress free survival (PFS) of the patients was 6.0 (0.5, 26.5) months, and the median overall survival was 16 (3, 103) months. There was no statistically significant difference in the PFS survival curve between patients treated first-line with darettuzumab and RRMM patients (χ2=3.676, P=0.055). The difference of PFS survival curve between patients with normal and impaired renal function was statistically significant (χ2=12.51, P=0.004). There was a statistically significant difference in the survival curve of patients treated with daletumab + bortezomib + dexamethasone and those treated with daletumab + dexamethasone (χ2=6.691, P=0.009). There was no statistically significant difference in PFS survival curves between patients with non-high risk and high-risk cytogenetic classification (χ2=0.328, P=0.567). There was no statistically significant difference in PFS survival curves among patients with M protein types of IgA, IgG, IgD, light chain, double clone and non-secretory (P>0.05). The main adverse reactions of the patients were infusion reaction and myelosuppression, of which 21 patients had adverse infusion reactions at the first infusion, 21 patients had leukopenia, 40 patients had anemia and 16 patients had thrombocytopenia. Conclusion Darettuzumab has good curative effect in MM patients, which can be used as the first-line treatment for newly diagnosed patients, improve the clinical prognosis of RRMM patients, and prolong the survival time of patients.

Abstract. Background:. Current guidelines recommend hepatocellular carcinoma (HCC) screening in high-risk populations. However, the ideal HCC screening interval and screening modality have not been determined. This study aimed to compare the screening efficacy among different modalities with various intervals. Methods:. PubMed and other nine databases were searched through June 30, 2021. Binary outcomes were pooled using risk ratio (RR) with 95% confidence intervals (CIs). Survival rates were also pooled using RR with 95% CIs because most eligible studies only provided the number of survival patients instead of hazard ratio. Results:. In all, 13 studies were included. Two random controlled trials (RCTs) and six cohort studies compared screening intervals for ultrasonography (US) screening and found no significant differences between shorter (3- or 4-month) and longer (6- or 12-month) screening intervals in terms of early HCC proportion, HCC significant mortality, 1-year survival rate; screening at 6-month interval significantly increased the proportion of early HCC (RR = 1.17, 95% confidence interval [CI]: 1.08–1.26) and prolonged the 5-year survival rate (RR = 1.39, 95% CI: 1.07–1.82) relative to the 12-month interval results. Three other RCTs and two cohort studies compared different screening modalities in cirrhosis or chronic hepatitis B, which indicated no statistical differences in the proportion of early HCC (RR = 0.89, 95% CI: 0.40–1.96) and HCC mortality (RR = 0.69, 95% CI: 0.23–2.09) between the biannual US and annual computed tomography (CT screening). Biannual US screening showed a lower proportion of early HCC than biannual magnetic resonance imaging (MRI) (RR = 0.60, 95% CI: 0.37–0.97) and biannual US combined with annual CT (RR = 1.31, 95% CI: 1.13–1.51) screening. The proportion of early HCC in the contrast-enhanced US group was slightly higher than that in the B-mode US (RR = 1.08, 95% CI: 1.00–1.23) group. Conclusions:. The evidence suggests that 6 months may be the best HCC screening interval for US screening. The effectiveness of CT and MRI is better than US during same screening intervals. However, MRI and CT are more expensive than US, and CT also can increase the risk of radiation exposure. The selection of CT or MRI instead of US should be carefully considered. Registration:. No. CRD42020148258 at PROSPERO website (https://www.crd.york.ac.uk/PROSPERO/).

Homeobox containing 1 (HMBOX1) is a transcription factor that was identified in 2006 from a cDNA library of the human pancreas. It belongs to the HNF gene class of the homeobox family. HMBOX1 is widely expressed in normal human tissues; however, its expression level is rather uneven. Homeobox members have been widely reported to participate in embryonic development and differentiation as well as in pathological and physiological processes. Although research on the role of HMBOX1 is still in its infancy, many reports have revealed its regulatory role in cell differentiation, immune regulation, inflammation, and tumor progression. HMBOX1 plays an important role in promoting the differentiation of bone marrow stromal stem cells (BMSCs) into endothelial cells and contributes to their physiological functions. As an immunoregulatory factor, HMBOX1 can significantly inhibit the inflammatory response in hepatocytes and NK cells and impede the infiltration of peripheral immune cells to the liver. In tumor development, HMBOX1 exerts diametrically opposite biological functions, inhibiting or promoting the process. HMBOX1 possesses complex and diverse biological functions. In this review, we provide a brief overview of the research on HMBOX1.

Abstract Background The mother–child inheritance of DNA methylation (DNAm) variations could contribute to the inheritance of disease susceptibility across generations. However, no study has investigated patterns of mother–child associations in DNAm at the genome-wide scale. It remains unknown whether there are sex differences in mother–child DNAm associations. Results Using genome-wide DNAm profiling data (721,331 DNAm sites, including 704,552 on autosomes and 16,779 on the X chromosome) of 396 mother–newborn pairs (54.5% male) from the Boston Birth Cohort, we found significant sex differences in mother–newborn correlations in genome-wide DNAm patterns (Spearman’s rho = 0.91–0.98; p = 4.0 × 10–8), with female newborns having stronger correlations. Sex differences in correlations were attenuated but remained significant after excluding X-chromosomal DNAm sites (Spearman’s rho = 0.91–0.98; p = 0.035). Moreover, 89,267 DNAm sites (12.4% of all analyzed, including 88,051 [12.5% of analyzed] autosomal and 1,216 [7.2% of analyzed] X-chromosomal sites) showed significant mother–newborn associations in methylation levels, and the top autosomal DNAm sites had high heritability than the genome-wide background (e.g., the top 100 autosomal DNAm sites had a medium h 2 of 0.92). Additionally, significant interactions between newborn sex and methylation levels were observed for 11 X-chromosomal and 4 autosomal DNAm sites that were mapped to genes that have been associated with sex-specific disease/traits or early development (e.g., EFHC2, NXY, ADCYAP1R1, and BMP4). Finally, 18,769 DNAm sites (14,482 [77.2%] on the X chromosome) showed mother–newborn differences in methylation levels that were significantly associated with newborn sex, and the top autosomal DNAm sites had relatively small heritability (e.g., the top 100 autosomal DNAm sites had a medium h 2 of 0.23). These DNAm sites were mapped to 2,532 autosomal genes and 978 X-chromosomal genes with significant enrichment in pathways involved in neurodegenerative and psychological diseases, development, neurophysiological process, immune response, and sex-specific cancers. Replication analysis in the Isle of Wight birth cohort yielded consistent results. Conclusion In two independent birth cohorts, we demonstrated strong mother–newborn correlations in whole blood DNAm on both autosomes and ChrX, and such correlations vary substantially by sex. Future studies are needed to examine to what extent our findings contribute to developmental origins of pediatric and adult diseases with well-observed sex differences.

Abstract As the Zhurong rover landed on the surface of Mars in 2021, it began a months-long collection of Mars data. Equipped with highly sensitive sensors, Zhurong is capable of being a meteorological station at the surface of Mars. The Mars Climate Station, one of the onboard sensors with high sensitivity, helps the Tianwen-1 lander to collect meteorological data at the Martian surface, via which the air temperature, atmospheric pressure, wind speed and direction are measured. In this paper, we present results of surface pressure, air temperature and wind data from the Mars Climate Station at Zhurong’s landing site. The data is collected in 176 solar days out of the entire rover’s mission time, 325 solar days. We use a trigonometric function to fit the relationship between the solar longitude (Ls) and the pressure, after which we compare the results with those of Viking I. Our analysis of the temperature shows that seasonal evolution is similar to the patterns concluded in previous Mars missions at different landing sites. We discover that wind speed appears the maximum in early summer near Zhurong’s landing site, and analyze the occurrence of dust storms by combining the data of wind and temperature. Our results provide some evidence of the seasonal changes in meteorological pattern at Tianwen-1’s landing site, south of Utopia Planitia. With the mission ongoing further, more results are expected in the future.

Background Tamarix chinensis Lour. is a 3–6-meter-tall small tree with high salt- and alkali- tolerance and aggressive invasiveness, mainly distributed in the eastern part of China in warm-temperate and subtropical climate zones, yet there is little information available regarding genetic diversity and population structure. Methods A total of 204 individuals of nine T. chinensis populations were investigated for genetic diversity and population structure using a set of 12 highly polymorphic microsatellite markers. Results The total number of alleles detected was 162, the average number of effective allele was 4.607, the average polymorphism information content (PIC) value of the 12 loci was 0.685, and the mean observed heterozygosity (Ho) and the mean expected heterozygosity (He) was 0.653 and 0.711, respectively. Analysis of molecular variance (AMOVA) showed a 5.32% genetic variation among T. chinensis populations. Despite a low population differentiation, Bayesian clustering analysis, discriminant analysis of principal components (DAPC) and the unweighted pair group method with arithmetic mean (UPGMA) clearly identified three genetic clusters correlated to the populations’ geographic origin: the northern populations including those from Yellow River Delta, the Fangshan (FS) population from Beijing, the Changyi (CY) population from Bohai Bay, the Huanjiabu (HHJ) population from Hangzhou Bay, and the remaining two populations from Hangzhou Bay. There was a significant relationship between the genetic distance and geographical distance of the paired populations. Gene flow (Nm) was 4.254 estimated from FST. Conclusion T. chinensis possessed high genetic diversity comparable to tree species, and although the population differentiation is shallow, our results classified the sampled populations according to sampling localities, suggesting the different origins of the study populations.

Abstract Background Parkinson’s disease (PD) is the second most common neurodegenerative disease in middle-aged and elderly populations, whereas there is no cure for PD so far. Novel animal models and medications await development to elucidate the aetiology of PD and attenuate the symptoms, respectively. Methods A neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), was used in the current study to establish a PD pathologic model in silkworms. The time required to complete specific behaviours was recorded. Dopamine content was detected by ultra-performance liquid chromatography (UPLC). The activity of insect tyrosine hydroxylase (TH) was determined using a double-antibody sandwich method. Oxidative stress was assessed by changes in antioxidant enzyme activity and the content of oxidative products. Results MPTP-treated silkworms were characterized by impaired motor ability, reduced dopamine content, and elevated oxidative stress level. The expression of TH, a dopamine biosynthetic enzyme within dopaminergic neurons in the brain, was significantly reduced, indicating that dopaminergic neurons were damaged. Moreover, MPTP-induced motility impairment and reduced dopamine level in the silkworm PD model could be rescued after feeding a combination of levodopa (L-dopa [LD]) and carbidopa (CD). MPTP-induced oxidative damage was also alleviated, in ways consistent with other PD animal models. Interestingly, administration of Lycium barbarum polysaccharide (LBP) improved the motor ability, dopamine level, and TH activity, and the oxidative damage was concomitantly reduced in the silkworm PD model. Conclusions This study provides a promising animal model for elucidating the pathogenesis of PD, as well as a relevant preliminary drug screening (e.g., LBP) and evaluation.

Introduction In recent decades, there has been a significant increase in childlessness. This paper analysed childlessness in China, specifically examining its socio and regional disparities.Methods With data from China’s 2020 population census, supplemented with data from China’s 2010 population census and 2015 inter-censual 1% population sample survey, we used a basic indicator of age-specific childlessness proportion, a decomposition method, and probability distribution models to analyse, fit and project childlessness.Results We presented age-specific childlessness proportions for women as a whole and by socioeconomic features, decomposition and projection results. The childlessness proportion increased markedly from 2010 to 2020, reaching 5.16% for women aged 49. The proportion is highest for city women, followed by township women, and is lowest among village women, at 6.29%, 5.50% and 3.72 % for women aged 49, respectively. The proportion for women aged 49 with high college education or above was 7.98%, and only 4.42% for women with junior high school education. The proportion also exhibits marked provincial discrepancies, and the total fertility rate is negatively correlated with childlessness at the province level. The decomposition results distinguished the different contribution of change in educational structure and change in childlessness proportion for subgroups to the total childlessness proportion change. It is projected that city women, women with high education will have higher childlessness proportion, and the proportion will further increase with the rapid increase in education level and urbanisation.Conclusions Childlessness has risen to a relatively high level, and varies among women with different characteristics. This should be taken into consideration in China’s countermeasures to reduce childlessness and curtail further fertility decline accordingly.

Abstract Objective To investigate the clinical features of multicentric reticulohistiocytosis (MRH). Methods The clinical manifestations, laboratory examination results and histologic characteristics of eleven patients with MRH were collected and compared with those of 33 patients with rheumatoid arthritis. Results In total, 72.7% of the MRH patients were women. The median age was 46 years (range 33–84 years). Diagnosed by specific pathologic features, all MRH patients exhibited cutaneous involvement. The dorsa of the hands, arms, face and auricle were the most commonly affected areas. Nodules were also located on the legs, scalp, trunk, neck, and even the hypoglossis and buccal mucosa. Ten MRH patients (90.9%) had symmetric polyarthritis. Compared with rheumatoid arthritis (RA) patients, MRH patients were more likely to have distal interphalangeal joint (DIP) involvement (63.6% vs 24.2%, P = 0.017) and less likely to have elbow (36.4% vs 72.7%, P = 0.003), ankle (45.5% vs 93.9%, P

Depression is of increasing concern as its prevalence increases. Our study's objective was to create and evaluate a nomogram to predict the likelihood that hypertension patients may experience depression. 13293 people with hypertension who were under 20 years old were chosen from the National Health and Nutrition Examination Survey (NHANES) database between 2007 and 2018 for this study. The training and validation sets were split up into the dataset at random in a 7:3 ratio. To find independent predictors, univariate and multivariate logistic regression were employed on the training set. Using information from the validation set, nomogram was subsequently created and internally validated. The effectiveness of the nomogram is assessed using calibration curve and receiver operator characteristic (ROC) curve. Combining univariate logistic regression analysis and multifactor logistic regression analysis, the results showed that age, sex, race, marital, education level, sleep time on workdays, poverty to income ratio, smoking, alcohol consumption, sedentary time and heart failure status were risk factors for hypertensive patients suffering from depression and were included in the nomogram model, and ROC analysis showed that the AUC of the training set was 0.757 (0.797-0.586), with a sensitivity of 0.586; the AUC of the test set was 0.724 (0.712-0.626), with a sensitivity of 0.626, which was a good fit. Decision curve analysis further confirms the value of nomogram for clinical application. In the civilian non-institutionalized population of the United States, our study suggests a nomogram that can aid in predicting the likelihood of depression in hypertension patients and aiding in the selection of the most effective treatments.

Background Sleep disturbance is an outcome of multiple factors including environmental and genetic influences. Job stress, a complex environmental factor, likely affects sleep quality, significantly reducing the quality of life of workers. Additionally, FK506 binding protein 51 (FKBP5) may be a pathogenic factor for sleep disturbance as it regulates hypothalamic–pituitary–adrenal (HPA) axis activity, where HPA axis has been found to be involved in the regulation mechanism of sleep and stress response. Objectives The main aim of this study was to investigate the association between job stress and FKBP5 gene polymorphism as well as their interaction with sleep disturbance in Chinese workers; to date, these relationships have not been explored. Methods This is a cross-sectional study. A total of 675 railway workers (53.8% male) completed a short Effort-Reward Imbalance questionnaire and the Pittsburgh Sleep Quality Index. The SNaPshot single nucleotide polymorphism (SNP) assay was carried out by screening for FKBP5 SNPs in every participant. Generalized multifactor dimensionality reduction (GMDR) was used to identify the strongest G×E interaction combination. Results The findings showed that job stress was significantly associated with sleep disturbance; specifically, scores on the PSQI subscales (sleep disturbance, sleep medication, and daytime dysfunction) exhibited significant differences between the two job stress groups (X2 = 18.10, p = 0.01). Additionally, the FKBP5 SNP rs1360780-TT (adjusted odds ratio [AOR] = 4.98, 95% confidence interval [CI] = 2.80–8.84) and rs3800373-CC genotype (AOR = 2.06, CI = 1.10–3.86) were associated with an increased risk of sleep disturbance. Job stress and rs1360780 and rs3800373 variants showed a high-dimensional interaction with sleep disturbance as determined by the GMDR model. Conclusion The FKBP5 gene may increase susceptibility to job stress and result in sleep disturbance, especially in the presence of negative work-related events. These findings contribute to the field of sleep disturbance prevention and treatment.

Objective To study the annual financial expenditure in blood stations with different scales, and to establish the regression equation between blood collection units and total expenditure. Methods The annual total expenditure, the per capita cost of serving population, as well as the collection units of whole blood and apheresis platelet of 24 blood stations were collected. The financial expenditure required for collecting 10 000U blood was calculated.The statistical analysis was carried out with SPSS statistical software. Results From 2017 to 2020, the total annual financial expenditure of 24 blood stations showed an upward trend. The total expenditure among blood stations was different. The per capita cost of servicing population in the areas where the 24 blood stations were located had been increasing year by year. The 24 blood stations were divided into two grades according to the blood collection volume as 50 000 U, and the relationship equation between the blood collection volume and the annual total expenditure had been established. After testing, each equation was effective(P

Abstract The present paper examines longitudinally how subjective perceptions about COVID-19, one’s community, and the government predict adherence to public health measures to reduce the spread of the virus. Using an international survey (N = 3040), we test how infection risk perception, trust in the governmental response and communications about COVID-19, conspiracy beliefs, social norms on distancing, tightness of culture, and community punishment predict various containment-related attitudes and behavior. Autoregressive analyses indicate that, at the personal level, personal hygiene behavior was predicted by personal infection risk perception. At social level, social distancing behaviors such as abstaining from face-to-face contact were predicted by perceived social norms. Support for behavioral mandates was predicted by confidence in the government and cultural tightness, whereas support for anti-lockdown protests was predicted by (lower) perceived clarity of communication about the virus. Results are discussed in light of policy implications and creating effective interventions.

Abstract Human papillomavirus (HPV) infection is the major etiological factor for cervical cancer. HPV prophylactic vaccines based on L1 virus-like particles have been considered as an effective prevention method. However, existing recombination vaccines are too expensive for developing countries. DNA vaccines might be a lower-cost and effective alternative. In this study, a plasmid (pcDNA3.1-HPV16-L1) and a co-expressing plasmid (pcDNA3.1-HPV16-L1-siE6) carried by attenuated Salmonella were constructed and their prevention and treatment effect on cervical cancer were observed, respectively. The results showed that pcDNA3.1-HPV16-L1 carried by attenuated Salmonella could induce the production of HPV16-L1 antibodies, IL-2 and INF-γ in mice serum, which presented its prevention effect on HPV. Subsequently, E6 and E7 gene silencing by pCG-siE6 inhibited the growth of cervical cancer both in vitro and in vivo. Furthermore, L1 up-regulation and E6/E7 down-regulation caused by co-expressing plasmid (pcDNA3.1-HPV16-L1-siE6) contributed to a significant anti-tumor effect on the mice. This study suggests that pcDNA3.1-HPV16-L1-siE6 carried by attenuated Salmonella has a synergistic effect of immune regulation and RNA interference in cervical cancer treatment.

Background The triglycerides-glucose index (TyG) and the triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) are simple indicators for assessing insulin resistance in epidemiological studies. We aimed to clarify the relationship between indicators of insulin resistance and prognosis in non-diabetic acute myocardial infarction (AMI) patients. Methods A total of 1,648 AMI patients without diabetes were enrolled from the Department of Cardiology, Zhongda Hospital, between 2012.03 and 2018.12. The medical history, laboratory and imaging data of patients were collected through the medical record system, and all-cause death events were recorded. Pearson analysis was used to study the correlation among different variables. Logistic regression analysis was used to analyze the predictive effect of TyG and TG/HDL-C in in-hospital death of AMI patients. Results 1. In AMI group, the TyG index was significantly increased in death groups compared to no-death groups (P = 0.025). TG/HDL-C was not significantly increased in the death group of AMI patients (P = 0.588). The patients were respectively divided into Q1-Q4 groups and T1-T4 groups according to the quartiles of TyG and TG/HDL-C. The trends of in-hospital mortality in the Q4 group of TyG and T4 group of TG/HDL-C were higher than in other groups, although these differences were not significant. 2. Pearson correlation analysis showed that TyG was positively correlated with lipid-related markers, including ApoB (r = 0.248, P

Forkhead box O transcriptional factors, especially FoxO1 and FoxO3a, play critical roles in physiologic and pathologic immune responses. However, the function of FoxO4, another main member of the FoxO family, in lymphoid cells is still poorly understood. Here, we showed that loss of FoxO4 in T cells augmented IFN-γ production of Th1 cells in vitro. Correspondingly, conditional deletion of FoxO4 in CD4+ T cells enhanced T cell–specific responses to Listeria monocytogenes infection in vivo. Genome-wide occupancy and transcriptomic analyses identified Dkk3 (encoding the Dickkopf-3 protein) as a direct transcriptional target of FoxO4. Consistent with the FoxO4-DKK3 relationship, recombinant DKK3 protein restored normal levels of IFN-γ production in FoxO4-deficient Th1 cells through the downregulation of lymphoid enhancer–binding factor 1 (Lef1) expression. Together, our data suggest a potential FoxO4/DKK3 axis in Th1 cell differentiation, providing what we believe to be an important insight and supplement for FoxO family proteins in T lymphocyte biology and revealing a promising target for the treatment of immune-related diseases.

Acidic nucleoplasmic DNA-binding protein 1 (And-1/WDHD1) as a natural chimerical protein, is characterized by containing the WD-repeat and the HMG-box motif families. And-1 is over-expressed in multiple tumors and involved in the whole cell cycle containing prereplication complex (Pre-RC) assembly, DNA replication, checkpoint activation, DNA repair and sister chromatid cohesion establishment. As a novel target for cell cycle regulation, And-1 can be used in the development of broad-spectrum anti-cancer drugs. This article focuses on the research on the structural characteristics, biochemical functions and potential roles of And-1 in cancer in recent years, in order to provide references for the further research of And-1 and the development of new drugs.

Abstract This paper examines whether compliance with COVID-19 mitigation measures is motivated by wanting to save lives or save the economy (or both), and which implications this carries to fight the pandemic. National representative samples were collected from 24 countries (N = 25,435). The main predictors were (1) perceived risk to contract coronavirus, (2) perceived risk to suffer economic losses due to coronavirus, and (3) their interaction effect. Individual and country-level variables were added as covariates in multilevel regression models. We examined compliance with various preventive health behaviors and support for strict containment policies. Results show that perceived economic risk consistently predicted mitigation behavior and policy support—and its effects were positive. Perceived health risk had mixed effects. Only two significant interactions between health and economic risk were identified—both positive.

Anxiety associated with the COVID-19 pandemic and home confinement has been associated with adverse health behaviors, such as unhealthy eating, smoking, and drinking. However, most studies have been limited by regional sampling, which precludes the examination of behavioral consequences associated with the pandemic at a global level. Further, few studies operationalized pandemic-related stressors to enable the investigation of the impact of different types of stressors on health outcomes. This study examined the association between perceived risk of COVID-19 infection and economic burden of COVID-19 with health-promoting and health-damaging behaviors using data from the PsyCorona Study: an international, longitudinal online study of psychological and behavioral correlates of COVID-19. Analyses utilized data from 7,402 participants from 86 countries across three waves of assessment between May 16 and June 13, 2020. Participants completed self-report measures of COVID-19 infection risk, COVID-19-related economic burden, physical exercise, diet quality, cigarette smoking, sleep quality, and binge drinking. Multilevel structural equation modeling analyses showed that across three time points, perceived economic burden was associated with reduced diet quality and sleep quality, as well as increased smoking. Diet quality and sleep quality were lowest among respondents who perceived high COVID-19 infection risk combined with high economic burden. Neither binge drinking nor exercise were associated with perceived COVID-19 infection risk, economic burden, or their interaction. Findings point to the value of developing interventions to address COVID-related stressors, which have an impact on health behaviors that, in turn, may influence vulnerability to COVID-19 and other health outcomes.

The exceptionally rich fossil record available for the equid family has provided textbook examples of macroevolutionary changes. Horses, asses, and zebras represent three extant subgenera of Equus lineage, while the Sussemionus subgenus is another remarkable Equus lineage ranging from North America to Ethiopia in the Pleistocene. We sequenced 26 archaeological specimens from Northern China in the Holocene that could be assigned morphologically and genetically to Equus ovodovi, a species representative of Sussemionus. We present the first high-quality complete genome of the Sussemionus lineage, which was sequenced to 13.4× depth of coverage. Radiocarbon dating demonstrates that this lineage survived until ~3500 years ago, despite continued demographic collapse during the Last Glacial Maximum and the great human expansion in East Asia. We also confirmed the Equus phylogenetic tree and found that Sussemionus diverged from the ancestor of non-caballine equids ~2.3–2.7 million years ago and possibly remained affected by secondary gene flow post-divergence. We found that the small genetic diversity, rather than enhanced inbreeding, limited the species’ chances of survival. Our work adds to the growing literature illustrating how ancient DNA can inform on extinction dynamics and the long-term resilience of species surviving in cryptic population pockets.

Abstract Elucidating the chemical structure of soil organic matter (SOM) is important for accurately evaluating the stability and function of SOM. Aboveground vegetation directly affects the quantity and quality of exogenous organic matter input into the soil through plant residues and root exudates, which in turn affects soil microbial species, community structure, and activity, and ultimately impacts the chemical structure of SOM. In this study, a 13C nuclear magnetic resonance technique was used to analyze the chemical structure characteristics of soil organic carbon (SOC) under various rates of straw returning combined with rotary tillage and under full straw mulching. The results showed that full straw returning with rotary tillage and full straw mulching more effectively increased the SOC content than reduced rate of straw returning (1/2 and 1/3 of full straw) with rotary tillage. The contents of alkyl C and alkoxy C in the functional groups of SOC under various straw returning treatments were increased compared with those under the treatment of maize stubble remaining in soil (CK). Furthermore, the contents of aromatic C and carboxyl C were decreased, which were consistent with the chemical shift changes of SOC. Compared with CK treatment, straw returning decreased the content of aromatic C in the functional groups of SOC, but increased the content of alkoxy C, which could be associated with the change in integral areas of absorption peaks of alkyl C and alkoxy C moving toward left and right, respectively. The content of total SOC was significantly positively (P

Abstract Background Colposcopy diagnosis and directed biopsy are the key components in cervical cancer screening programs. However, their performance is limited by the requirement for experienced colposcopists. This study aimed to develop and validate a Colposcopic Artificial Intelligence Auxiliary Diagnostic System (CAIADS) for grading colposcopic impressions and guiding biopsies. Methods Anonymized digital records of 19,435 patients were obtained from six hospitals across China. These records included colposcopic images, clinical information, and pathological results (gold standard). The data were randomly assigned (7:1:2) to a training and a tuning set for developing CAIADS and to a validation set for evaluating performance. Results The agreement between CAIADS-graded colposcopic impressions and pathology findings was higher than that of colposcopies interpreted by colposcopists (82.2% versus 65.9%, kappa 0.750 versus 0.516, p 0.05). The CAIADS also demonstrated a superior ability in predicting biopsy sites, with a median mean-intersection-over-union (mIoU) of 0.758. Conclusions The CAIADS has potential in assisting beginners and for improving the diagnostic quality of colposcopy and biopsy in the detection of cervical precancer/cancer.

BackgroundThe online market is getting popular today, and consumers' preferences about products are revealed differently in online and offline markets. Especially, fresh food purchasing online is very different from non-food products due to its unique features such as perishability, low cost and frequent purchases, low value-volume ratio, and highly relevance to safety and health. However, studies on online fresh food are rather few, and this study will fill the gap by investigating consumers' preferences for fresh food online purchasing.MethodsUsing unique data observed from online stores, we conduct a hedonic analysis of fresh produce online market using apple market in China, avoiding hypothetical bias. Propensity Score Matching is used to check the online promotion effects. The data are apples transactions from Jingdong JD e-commerce platform with sample size 8,200, observed across six weeks from 11/26/2018 to 12/31/2018. Variables used include prices, promotions, varieties, places of origin, fruit size, labeled as organic or green food, watercore label, and customer reviews for the products as well as for the venders.ResultsWe found place of origin, food safety and eco-certificates, and sensory features all influence apple prices which reflect consumer preferences. In addition to product features, store features such as former customers' review for the store, a video post of the product, and other latent product features through former customers' review for the product quality also influence consumers' preference reflected by price.ConclusionsIn additional to product intrinsic features, consumer show preferences and valuation for online market special features.

Background: Despite strengthened efforts on human immunodeficiency virus (HIV) prevention and control, new HIV infections continue to increase among men who have sex with men (MSM) in China. Pre-exposure prophylaxis (PrEP), a highly effective HIV-prevention tool, has recently been included in China's Action Plan of HIV Prevention and Control. To promote future PrEP implementation, this study aims to identify the barriers and facilitators in PrEP use intention among MSM in China. Methods: In 2018, a cross-sectional survey was conducted among 300 MSM in Nanjing, Jiangsu Province. Questions on demographics, sexual behavior (including a seven-item high-risk behavior index), PrEP use intention, PrEP-related awareness and accessibility, and a seven-item public HIV stigma scale were included in the questionnaire. Bivariate and multivariate logistic regression analyses were conducted to identify factors associated with PrEP use intention. Results: Overall, 44.67% of the participants had more than two male sexual partners and 5.56% had HIV-positive sexual partners. Only 57.00% had heard of PrEP and only four (1.33%) participants had used PrEP. However, 75.34% expressed the willingness to use oral PrEP if its efficacy was assured. The beliefs that “PrEP can prevent HIV if taken as prescribed” (adjusted odds ratio (AOR) = 4.84, P < 0.001) and “PrEP can be scaled up in the community” (AOR = 3.24, P < 0.001) were positively associated with oral PrEP use intention. Concerns of side effects were negatively associated with oral PrEP use intention (AOR = 0.32, P = 0.006). Further, 77.00% of the participants would choose injectable or implanted PrEP instead of oral PrEP. One of the PrEP stigma items, “Not certain if doctors can prescribe PrEP if I go to the clinic” was positively associated with the intention to use injectable or implanted PrEP (AOR = 3.03). The items “Heard of PrEP” (AOR = 2.74) and “PrEP can prevent HIV if taken as prescribed” (AOR = 2.65) were also positively related to the intention to use injectable or implanted PrEP. The most common concerns regarding PrEP use were efficacy (44.67%) and side effects (38.67%). The most common reasons for using injectable and implanted PrEP were adherence (81.94% and 77.86%, respectively) and privacy concerns (56.48% and 55.00%, respectively). Affordable price and coverage by health insurance were the driving factors for PrEP use. Conclusion: Given the low level of awareness of PrEP-related information in China, it's necessary to provide interventions for high-risk individuals and communities, in order to increase their awareness and knowledge of PrEP. Furthermore, additional alternatives to HIV prevention, such as long-acting injectable or implanted PrEP, should be investigated to reduce the risk of HIV infection in at-risk MSM. Even if this programme could be approved by the National Medical Products Administration of China and implemented, a supportive social environment for MSM is essential during its implementing.

Abstract. Background. Despite the recent advances in treatments for rheumatoid arthritis (RA), there are still unmet needs in disease outcomes. This study aimed to analyze the satisfaction with drug therapies for RA according to the levels of disease severity (patient-assessed) and proportions of treatment cost to household income. Methods. This was a subgroup study of a cross-sectional study in patients with RA and their physicians. The patients were subdivided into different subgroups based on their self-assessed severity of RA and on the proportions of treatment cost to household income (50%). The Treatment Satisfaction Questionnaire for Medication version II was used to assess patients’ treatment satisfaction. Results. When considering all medications, effectiveness, convenience, and global satisfaction scores were lower in the severe and moderate RA subgroups than those in the mild and extremely mild RA subgroups (all P 50% subgroup (all P 50% subgroups (F = 12.646, P = 0.005). Global satisfaction score was higher in the

Abstract Background Microbes are greatly associated with human health and disease, especially in densely populated cities. It is essential to understand the microbial ecosystem in an urban environment for cities to monitor the transmission of infectious diseases and detect potentially urgent threats. To achieve this goal, the DNA sample collection and analysis have been conducted at subway stations in major cities. However, city-scale sampling with the fine-grained geo-spatial resolution is expensive and laborious. In this paper, we introduce MetaMLAnn, a neural network based approach to infer microbial communities at unsampled locations given information reflecting different factors, including subway line networks, sampling material types, and microbial composition patterns. Results We evaluate the effectiveness of MetaMLAnn based on the public metagenomics dataset collected from multiple locations in the New York and Boston subway systems. The experimental results suggest that MetaMLAnn consistently performs better than other five conventional classifiers under different taxonomic ranks. At genus level, MetaMLAnn can achieve F1 scores of 0.63 and 0.72 on the New York and the Boston datasets, respectively. Conclusions By exploiting heterogeneous features, MetaMLAnn captures the hidden interactions between microbial compositions and the urban environment, which enables precise predictions of microbial communities at unmeasured locations.